rs369643771

Variant names:

• chr17-42811789-C-T
• rs369643771
• NM_001313998.2:c.1050G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-42811789-C-T
• chr17-42811789-C-G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001313998.2(BECN1):​c.1050G>A​(p.Pro350Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000627 in 1,610,608 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (2 hom., cov: 32)
  • Exomes 𝑓: 0.000061 (3 hom.)
• Consequence: BECN1 NM_001313998.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.21
• Publications: 1 publications found

Genes affected

BECN1 (HGNC:1034): (beclin 1) This gene encodes a protein that regulates autophagy, a catabolic process of degradation induced by starvation. The encoded protein is a component of the phosphatidylinositol-3-kinase (PI3K) complex which mediates vesicle-trafficking processes. This protein is thought to play a role in multiple cellular processes, including tumorigenesis, neurodegeneration and apoptosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

CNTD1 (HGNC:26847): (cyclin N-terminal domain containing 1) Predicted to be involved in reciprocal meiotic recombination. Predicted to act upstream of or within spermatogenesis. Predicted to be active in site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 17-42811789-C-T is Benign according to our data. Variant chr17-42811789-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3133659.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.21 with no splicing effect.
• BS2: High AC in GnomAd4 at 12 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001313998.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BECN1	NM_001313998.2	MANE Select	c.1050G>A	p.Pro350Pro	synonymous	Exon 11 of 12	NP_001300927.1	A0A024R1X5
	BECN1	NM_003766.5		c.1050G>A	p.Pro350Pro	synonymous	Exon 11 of 12	NP_003757.1	A0A024R1X5
	BECN1	NM_001313999.1		c.1042-861G>A		intron	N/A	NP_001300928.1	W0FFG4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BECN1	ENST00000590099.6	TSL:1 MANE Select	c.1050G>A	p.Pro350Pro	synonymous	Exon 11 of 12	ENSP00000465364.1	Q14457
	BECN1	ENST00000361523.8	TSL:1	c.1050G>A	p.Pro350Pro	synonymous	Exon 11 of 12	ENSP00000355231.3	Q14457
	BECN1	ENST00000590764.1	TSL:2	c.77G>A	p.Arg26His	missense	Exon 2 of 3	ENSP00000468597.1	K7ES83

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152180 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000101 AC: 25 AN: 247926 AF XY: 0.000127

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000598

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000220

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000888

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000610 AC: 89 AN: 1458310 Hom.: 3 Cov.: 30 AF XY: 0.0000813 AC XY: 59 AN XY: 725508

African (AFR) AF: 0.0000603 AC: 2 AN: 33176

American (AMR) AF: 0.0000459 AC: 2 AN: 43584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25932

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39676

South Asian (SAS) AF: 0.000783 AC: 67 AN: 85582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1110992

Other (OTH) AF: 0.0000830 AC: 5 AN: 60220

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152298 Hom.: 2 Cov.: 32 AF XY: 0.0000940 AC XY: 7 AN XY: 74478

African (AFR) AF: 0.00 AC: 0 AN: 41552

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.0000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.3
DANN	Benign	0.70
PhyloP100		-4.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs369643771; hg19: chr17-40963807; COSMIC: COSV100162117; COSMIC: COSV100162117;